Relative affinity of quazepam for type-1 benzodiazepine receptors in brain

Abstract

Quazepam and its major metabolite, 2-oxoquazepam, were the first benzodiazepine (BZ) compounds shown to be capable of differentiating between central nervous system (CNS) subtypes of BZ receptors. Initial studies suggested that quazepam preferentially binds to the BZ1-receptor population with high affinity at relatively low doses. Subsequent binding experiments, performed in both human and rodent brain, confirmed this hypothesis for both the parent compound and its principal metabolite. Autoradiographic studies revealed a differential distribution of BZ1 and BZ2 receptors within regions of the brain associated with behavior, sensory input, control of movement, and coordination. BZ1 receptors are concentrated in specific, well-localized regions of the brain. BZ2 receptors are more widespread and diffusely localized throughout most brain regions. These observations suggest that a selective BZ1 agent such as quazepam might have a different pharmacologic profile than other nonselective benzodiazepines. Restricting the number of sites where BZ drugs act has been proposed as a strategy for producing a more circumscribed therapeutic effect; the BZ1 selectivity of quazepam embodies this concept.